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Integrator enforces the fidelity of transcriptional termination at protein-coding genes
Integrator regulates the 3′-end processing and termination of multiple classes of noncoding RNAs. Depletion of INTS11, the catalytic subunit of Integrator, or ectopic expression of its catalytic dead enzyme impairs the 3′-end processing and termination of a set of protein-coding transcripts termed I...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8565846/ https://www.ncbi.nlm.nih.gov/pubmed/34730992 http://dx.doi.org/10.1126/sciadv.abe3393 |
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author | Dasilva, Lucas Ferreira Blumenthal, Ezra Beckedorff, Felipe Cingaram, Pradeep Reddy Gomes Dos Santos, Helena Edupuganti, Raghu Ram Zhang, Anda Dokaneheifard, Sadat Aoi, Yuki Yue, Jingyin Kirstein, Nina Tayari, Mina Masoumeh Shilatifard, Ali Shiekhattar, Ramin |
author_facet | Dasilva, Lucas Ferreira Blumenthal, Ezra Beckedorff, Felipe Cingaram, Pradeep Reddy Gomes Dos Santos, Helena Edupuganti, Raghu Ram Zhang, Anda Dokaneheifard, Sadat Aoi, Yuki Yue, Jingyin Kirstein, Nina Tayari, Mina Masoumeh Shilatifard, Ali Shiekhattar, Ramin |
author_sort | Dasilva, Lucas Ferreira |
collection | PubMed |
description | Integrator regulates the 3′-end processing and termination of multiple classes of noncoding RNAs. Depletion of INTS11, the catalytic subunit of Integrator, or ectopic expression of its catalytic dead enzyme impairs the 3′-end processing and termination of a set of protein-coding transcripts termed Integrator-regulated termination (IRT) genes. This defect is manifested by increased RNA polymerase II (RNAPII) readthrough and occupancy of serine-2 phosphorylated RNAPII, de novo trimethylation of lysine-36 on histone H3, and a compensatory elevation of the cleavage and polyadenylation (CPA) complex beyond the canonical polyadenylation sites. 3′ RNA sequencing reveals that proximal polyadenylation site usage relies on the endonuclease activity of INTS11. The DNA sequence encompassing the transcription end sites of IRT genes features downstream polyadenylation motifs and an enrichment of GC content that permits the formation of secondary structures within the 3′UTR. Together, this study identifies a subset of protein-coding transcripts whose 3′ end processing requires the Integrator complex. |
format | Online Article Text |
id | pubmed-8565846 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-85658462021-11-17 Integrator enforces the fidelity of transcriptional termination at protein-coding genes Dasilva, Lucas Ferreira Blumenthal, Ezra Beckedorff, Felipe Cingaram, Pradeep Reddy Gomes Dos Santos, Helena Edupuganti, Raghu Ram Zhang, Anda Dokaneheifard, Sadat Aoi, Yuki Yue, Jingyin Kirstein, Nina Tayari, Mina Masoumeh Shilatifard, Ali Shiekhattar, Ramin Sci Adv Biomedicine and Life Sciences Integrator regulates the 3′-end processing and termination of multiple classes of noncoding RNAs. Depletion of INTS11, the catalytic subunit of Integrator, or ectopic expression of its catalytic dead enzyme impairs the 3′-end processing and termination of a set of protein-coding transcripts termed Integrator-regulated termination (IRT) genes. This defect is manifested by increased RNA polymerase II (RNAPII) readthrough and occupancy of serine-2 phosphorylated RNAPII, de novo trimethylation of lysine-36 on histone H3, and a compensatory elevation of the cleavage and polyadenylation (CPA) complex beyond the canonical polyadenylation sites. 3′ RNA sequencing reveals that proximal polyadenylation site usage relies on the endonuclease activity of INTS11. The DNA sequence encompassing the transcription end sites of IRT genes features downstream polyadenylation motifs and an enrichment of GC content that permits the formation of secondary structures within the 3′UTR. Together, this study identifies a subset of protein-coding transcripts whose 3′ end processing requires the Integrator complex. American Association for the Advancement of Science 2021-11-03 /pmc/articles/PMC8565846/ /pubmed/34730992 http://dx.doi.org/10.1126/sciadv.abe3393 Text en Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution license (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Biomedicine and Life Sciences Dasilva, Lucas Ferreira Blumenthal, Ezra Beckedorff, Felipe Cingaram, Pradeep Reddy Gomes Dos Santos, Helena Edupuganti, Raghu Ram Zhang, Anda Dokaneheifard, Sadat Aoi, Yuki Yue, Jingyin Kirstein, Nina Tayari, Mina Masoumeh Shilatifard, Ali Shiekhattar, Ramin Integrator enforces the fidelity of transcriptional termination at protein-coding genes |
title | Integrator enforces the fidelity of transcriptional termination at protein-coding genes |
title_full | Integrator enforces the fidelity of transcriptional termination at protein-coding genes |
title_fullStr | Integrator enforces the fidelity of transcriptional termination at protein-coding genes |
title_full_unstemmed | Integrator enforces the fidelity of transcriptional termination at protein-coding genes |
title_short | Integrator enforces the fidelity of transcriptional termination at protein-coding genes |
title_sort | integrator enforces the fidelity of transcriptional termination at protein-coding genes |
topic | Biomedicine and Life Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8565846/ https://www.ncbi.nlm.nih.gov/pubmed/34730992 http://dx.doi.org/10.1126/sciadv.abe3393 |
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